Abstract
The microtubule assembly process has been extensively studied, but the underlying molecular mechanism remains poorly understood. The structure of an artificially generated sheet polymer that alternates two types of lateral contacts and that directly converts into microtubules, has been proposed to correspond to the intermediate sheet structure observed during microtubule assembly. We have studied the self-assembly process of GMPCPP tubulins into sheet and microtubule structures using thermodynamic analysis and stochastic simulations. With the novel assumptions that tubulins can laterally interact in two different forms, and allosterically affect neighboring lateral interactions, we can explain existing experimental observations. At low temperature, the allosteric effect results in the observed sheet structure with alternating lateral interactions as the thermodynamically most stable form. At normal microtubule assembly temperature, our work indicates that a class of sheet structures resembling those observed at low temperature is transiently trapped as an intermediate during the assembly process. This work may shed light on the tubulin molecular interactions, and the role of sheet formation during microtubule assembly.
Highlights
Microtubules are one of the three major cytoskeleton components in eukaryotic cells [1,2]
For DGSh2DGTu.0 the percentage of ribbon structures starts with a relative high value, decreases with time
At low temperatures, the sheet bond is more stable than the tube bond (DGSh{DGTuv0)
Summary
Microtubules are one of the three major cytoskeleton components in eukaryotic cells [1,2]. They are hollow cylinders consisting of about 13 parallel protofilaments (PF) formed by the head-to-tail assembly of ab-tubulin heterodimers. Microtubules play important roles in many eukaryotic cellular processes, including intracellular transport, cell motility, mitosis and meiosis. The regulation of microtubule dynamics has been shown to be both of great biological significance during cell division, and of outstanding pharmaceutical value in tumor therapy. Taxolß, the most widely used anticancer agent, targets tubulin and alters microtubule dynamics resulting in mitotic arrest. Studying the microtubule assembly/disassembly processes is of great relevance for both biological and pharmaceutical purposes
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